Hypertensive cardiovascular disease affects approximately 40-60 million Americans and is thought to be a primary contributor to coronary artery disease and stroke which collectively account for most of the cardiovascular deaths in this country. Over a period of many years it has become apparent that the regulation of arterial blood pressure is intimately linked to body salt and water balance. Recent evidence suggests that several peptides derived from the N-terminal portion of the atrial natriuretic factor (ANF) prohormone also play an important role in regulating kidney function and arterial blood pressure. The long term goals of the present application are to obtain a better understanding of the role of ANF and ANF prohormone peptides in the regulation of kidney function, blood volume and blood pressure. The applicant will carry out studies to investigate the role of nitric oxide, endothelin and adenosine on the paracrine regulation of ANF and proANF release. The applicant has shown previously that proANF 1-30 produces natriuresis and hypotension through, as yet, undefined mechanisms. He proposes to investigate four likely potential mechanisms that may contribute to the natriuretic properties of this peptide. These include prostaglandin synthesis, alterations in hemodynamics, cGMP synthesis and changes in activity of the renin-angiotensin-aldosterone system. Finally, the applicant proposes to develop specific antibodies to the rat forms of proANF 1-30 and 31-67 to provide accurate measurements of these peptides in rat tissues and plasma and to employ as antagonists in dissecting out the contribution of these peptides to natriuretic/anti-hypertensive mechanisms which are activated as part of the physiological response to volume expansion and chronic hypertension.